This research proposal is an investigation of the local control of alveolar bone metabolism using the precisely timed and localized events of premolar tooth eruption in the dog. In this model system eruption of mandibular premolars is dependent upon the presence of the dental follicle, is independent of the tooth or its development and is characterized by a coordinated resorption of alveolar bone above and formation of bone below the space occupied by the tooth. Recent work from our laboratories has shown that the follicle is adjacent to these polarized areas of alveolar bone formation and resorption, that these respective activities depend upon the follicle and that its coronal aspect next to the resorption area is infiltrated by mononuclear cells just prior to eruption. These cells are monocytes by ultrastructural and cytochemical criteria and have characteristics of pre-osteoclasts. Biochemical studies show that the collagen and proteoglycan content of the follicle change during eruption and that characteristic sialoproteins herald eruption. One of 95k exhibits properties of a structural protein and reduces in amount with eruption. Three of 20-25k appear when eruption begins. Our hypothesis is that these events are related to eruption and that completion of enamel (crown) formation signals eruption through changes in the enamel organ. This proposal explores this hypothesis by examining the role of the enamel organ and collagen in early and late prefunctional eruption and biochemical changes in the enamel organ, basal and coronal areas of the follicle and characteristic follicle proteins during eruption. These studies will employ microsurgical, morphological, biochemical and molecular biological methods to define chemical and molecular events in tooth eruption. Future studies will examine strategies for surgical and molecular interceptions of tooth eruption and alveolar bone metabolism in this in vivo model. The proposed research has significance not only for better clinical management of ectopic and retarded eruption but also for better management of alveolar bone metabolism in development and disease.